1. Field of the Invention
The present invention relates to non-invasive apparatuses and methods for determining bone strength in vivo and, most particularly, to such apparatuses and methods that use ultrasonic energy for determining bone strength in vivo.
2. Discussion of Related Art
Osteoporosis is a complex, incompletely understood disease that affects the entire skeletal system. Herein, the term "osteoporosis" is used to refer to a variety of conditions all characterized by a degradation of bone strength ultimately leading to fracture.
To understand bone strength, one must understand bone architecture and composition. Although all bones comprise the same structural constituents of collagen, crystallized calcium and interstitial fluid, individual bones have architectures that differ significantly. The skeletal system can be generally divided into two categories of bones: cortical (compact) bone and cancellous (spongy) bone. Most bones in the body contain both categories, the compact cortical bone forming an outer shell surrounding a core of spongy cancellous bone. Cancellous bone is in the form of a three-dimensional lattice made of plates and columns (called trabeculae), and an interstitial fluid composed of red and yellow marrow and traces of other substances.
Recent research suggests that the deterioration of the mechanical strength of bone results from three different, yet interrelated, mechanisms. First, and most widely recognized, is the loss of bone mass which occurs in all individuals beginning in the third decade of life. The literature conclusively demonstrates the diminution of bone strength with loss of bone mass. See. e.g., Goldstein, S. A., "The Mechanical Properties of Trabecular Bone: Dependence on Anatomic Location and Function," J.Biomechanics, vol. 20, No. 11/12. pp. 1055-1061, 1987.
The second potentially important mechanism for deterioration of bone strength is the deterioration of the quality of the bone matrix itself. Recently discovered evidence suggests that biochemical stability of collagen in trabecular bone declines with age. See, Oxlund, H., Mosekilde, L., Ortoft, G., "Alterations in the Stability of Collagen from Human Trabecular Bone with Respect to Age," (abstract #97), Proceedings of the International Symposium on Osteoporosis, Ed., J. Jensen, B. Riis, C. Christiansen, Aalborg, Denmark, September 27-October 2, 1987. Furthermore, the collagen content of trabecular bone appears to be reduced in women with osteoporosis. Birkenhaager, D. H., "A Significant Lack of Collagen in Osteoporotic Bone," (abstract #111), Proceedings of the International Symposium on Osteoporosis, Ed., J. Jensen, B. Riis, C. Christiansen, Aalborg, Denmark, September 27-October 2, 1987. These references suggest a weakening of the protein binding the trabecular matrix, irrespective of bone mass. The strength of bone is crucial in determining whether a person will suffer osteoporotic fracture in the absence of trauma.
A third mechanism for the deterioration of bone strength has been identified as osteoporosis-related changes in trabecular architecture, even when accompanied by little or no measurable loss of bone mass. See, e.g., Kleerekoper, M., et al., "The Role of Three-Dimensional Trabecular Microstructure in the Pathogenesis of Vertebral Compression Fractures," Calcif. Tissue Int., 37:594-597, 1985.
These references identify three aspects of osteoporosis related changes in bone architecture. The first is unrepaired fatigue damage, fatigue being caused by repeated cyclings of stress on a bone. Such repeated cyclings cause fatigue damage and the strength of the bone is degraded when such fatigue damage is not repaired. Incomplete repair of fatigue damage can further decrease bone strength when damaged bone has been resorbed but not yet replaced with new bone. The second is deterioration of trabecular architecture, such as a decrease in the number of trabeculae between plates in cancellous bone which occurs in some women during menopause. The third is osteoid accumulation which is a result of collagen exhibiting a lack of calicification. None of these factors that degrade the strength of bone is necessarily characterized by a loss of bone mass. For example, the loss of trabecular columns between trabecular plates appears to reduce bone strength more than can be accounted for by a loss of bone mass alone.
In the past, various practices have been employed for the detection and evaluation of bone disease. Practice patterns vary regionally and by medical speciality. Physician specialists in obstetrics, gynecology, endocrinology, nutrition, internal medicine, orthopedics, radiology, nuclear medicine, family and general practice see and take an interest in bone disease. Depending upon their interests, such physicians may use some or all of the following bone health assessment techniques.
One assessment technique is a physical exam in which particular attention is paid to the structure of the spine. Complaints of sharp back pain and/or obvious curvature (kyphosis) is symptomatic of later stages of bone diseases, such as osteoporosis.
A second assessment technique is risk factor assessment in which a patient's medical and family history is surveyed and/or personal habits, such as smoking, alcohol consumption and diet, are analyzed to assess the relative risk of osteoporotic fracture. Although widely considered a possibility, conclusive evidence of the predominance of particular risk factors as predictors of bone disease is unsubstantiated. J. T. Citron, et al., "Prediction of Peak Prememenopausal Bone Mass Using a Scale of Weighted Clinical Variables," Proceedings of the International Symposium on Osteoporosis, September/October, 1987, Denmark, Editors: J. Jensen, B. Riis, C. Christiansen, Abstract #17.
A third assessment technique involves blood and urine chemistries in which chemical analysis of blood and urine is conducted to determine the presence of calcium and other factors related to bone metabolism. Although clearly related to bone metabolism, such chemistries are not necessarily indicative of bone strength.
A fourth method involves bone mass measuring techniques which measures radiation passed through all or a desired portion of a skeletal system as an indication as to the bone mass density of the bone being tested. Such bone mass measurement techniques are described in Peck, et al., "Physicians Resource Manual On Osteoporosis: A Decision Making Guide," National Osteoporosis Foundation, pp. 14-16, 1987, and include X-ray, single photon absorptiometry, dual photon absorptiometry and quantitative computed tomography.
Although the foregoing techniques do provide information about bones in vivo, they provide insufficient information to determine the strength of bone reliably in all cases. For example, the bone mass measuring techniques provide information concerning the mass of the bone but not its architecture and both factors are important in assessing the strength of a bone. A more effective assessment of osteoporotic fracture risk requires a more direct assessment of strength of bone. This is the motivation for the ultrasonic measurement of bone strength.
Sound is a traveling mechanical vibration. As it propagates, the vibration interacts with the mechanical properties of the medium and becomes progressively altered. By observing the differences between mechanical vibrations transmitted into bone and the mechanical vibrations after an ultrasonic signal has propagated a known distance through the bone, it is often possible to determine some of the mechanical properties of the bone.
Before discussing the specific application of ultrasound to the measurement of bone strength, it is important to review certain underlying physical concepts. Strain in a particular direction (which will be denoted as "X"), is the deformation an object exhibits when subjected to stress in that particular direction (which will be denoted as "F"). For example, strain X can be expressed as the percentage by which a bone shortens when compressed by force F. The elastic modulus E, associated with that particular direction, simply tells how much an object will deform when subjected to a specific amount of stress (F). The elastic modulus E is large for a strong object which exhibits little strain when subjected to a large force F. A weak object has a small elastic modulus E and will exhibit a large strain even when a small stress is applied. The three values can be related as follows: ##EQU1##
When a bone, having a constant elastic modulus E, is subjected to a stress F in a particular direction it deforms by the amount X in that same direction as determined by equation 1, so long as the stress is not so large as to cause plastic deformation or permanent alteration of the bone. The onset of fracture is that level of strain for which the bone no longer returns to its original state when the stress causing the strain is removed. A fracture can be either an outright break or the more subtle damage of stress fracture. X.sub.T is this threshold value of strain at which fracture begins to occur. F.sub.T is the corresponding stress leading to this strain. Then, from the stress/strain relationship above: EQU F.sub.T =E*X.sub.T ( 2)
To predict imminent fracture of a bone, one must determine either: (a) whether the maximum strain which the bone will exhibit as a result of the environment will exceed X.sub.T ; or (b) whether the maximum stress experienced as a result of the environment will exceed F.sub.T. Of course, predicting imminent fracture with either of these bone characteristics is academic since one cannot determine F.sub.T or X.sub.T. Similarly, one cannot measure the maximum stress that a subject's activities will cause or the maximum deformation that will result.
An alternative approach is to note that as a bone becomes weaker, it will exhibit greater strain X when subjected to a given stress F than will a stronger bone subjected to the same stress. The elastic modulus E should therefore decline as a bone becomes weaker. The elastic modulus can therefore be taken as an important component of a bone's likelihood to fracture.
The mechanics of solids relate the velocity of an ultrasonic signal to the stress/strain relationship discussed above. The velocity of longitudinal sound V in a given direction through a solid such as bone is: ##EQU2## where E is the elastic modulus in the direction under consideration; and r is the mass density of bone expressed, for example, in units of grams/cc. See, Abendschein, W., Hyatt, G. W., "Ultrasonic and Selected Physical Properties of Bone," Clin. Orthop. Rel. Res., 69:294-301, 1970.
Aging and certain diseases cause a decline in both the bone density r and the bone strength. Deterioration in bone strength is manifest as a decline in elastic modulus E. There is still insufficient information in equation 3, however, to tell how the velocity of sound will change in the face of deteriorating bone condition.
What is missing is the relationship between the elastic modulus E and the density r in bone. The elastic modulus has been shown empirically to be proportional to the square of the density r: EQU E=K*r.sup.2 ( 4)
See, e.g., Rice, J. C., Cowin, S. C., Bowman, J. A., "On The Dependence of the Elasticity and Strength of Cancellous Bone on Apparent Density," J. Biomechanics (in press), 1988.
The proportionality constant K has a physical interpretation. The primary structural constituents of bone are collagen fibrils, crystallized calcium (apatite), and an interstitial viscous fluid (marrow). Different relative proportions of each result in different values for the density. However, as discussed above, for a particular density r the same region of the same bone in different individuals (or the same individual at different stages of life) can possess different bone strengths; that is, the bone can have the same density r but different elastic modulus E. This is accounted for by a different bone quality factor K.
Much of this difference lies in the microscopic architecture of the bone itself. See, e.g., M. Kleerekoper, et al., "The Role of Three-Dimensional Trabecular Microstructure in the Pathogenesis of Verterbral Compression Fractures," Calcif. Tissue Int., 37:594-597, 1985. For example, one can pulverize bone and then compact it into a cylindrical shape to create a very high density object with almost no strength at all. Indeed, for a time after suffering a fracture associated with osteoporosis, crushed vertebra often exhibit higher mass density than adjacent normal vertebra when measured with X-ray, CT or dual photon devices. See, Hui, S. L., Slemenda, C. W., Johnston, C. C., Appledorn, C. R., "Effects of Age and Menopaure on Vertrebal Bone Density," Bone and Mineral, 2:141-146, 1987 and Ott, S. M., "Noninvasive Measurements of Bone Mass," Osteoporosis: Current Concepts, Report of the 7th Ross Conference on Medical Research, Charleston, SC, April 23-25, 1986, 22-24.
Another potentially important determinant of the bone quality factor K is the quality of the bone matrix itself. As explained above, the biochemical stability of collagen in trabecular bone declines with age. Furthermore, the collagen content of trabecular bone appears to be lower in women with osteoporosis. Both results suggest a weakening of the protein binding the trabecular matrix. Still further, bone quality factor K deteriorates as a result of unrepaired fatigue damage or osteoid accumulation.
The bone quality factor K, then, appears to be a measure of structural quality, indicating bone architecture and the quality of the bone matrix. For a given density r, the higher the bone quality factor K, the stronger the bone.
To understand how this relates to ultrasound, substitute the equation four (4) for the elastic modulus E in the expression for the velocity of sound V in equation (3). The elastic modulus E then disappears leaving: ##EQU3##
Now it becomes clear that bone deterioration resulting in a decrease in either the bone quality factor K or density r causes a decrease in the velocity V, because the mass density r no longer appears in a denominator as it did in the earlier expression for velocity V.
Radiological devices that measure only the density r of bone yield only part of the information needed to characterize the mechanical properties of bone. No information about the physical architecture of the bone is present. In contrast, the velocity of sound yields a quantity related to both the density r and the structural quality as represented by the bone quality factor K.
It appears, then, that the velocity by itself can serve as a measure of bone quality. Further, the velocity might also serve as an approximate indicator of the susceptibility of a bone to fracture. However, the accuracy of any indicator will be compromised by other uncontrollable factors which are difficult to quantify. See, Wasnich, R. D., "Fracture Prediction With Bone Mass Measurements," Osteoporosis Update 1987, Ed., H. K. Genant, Radiology Research and Education Foundation, San Francisco, CA, 95-101, 1987. These uncontrollable factors include, for example, range of physical activity of the individual; muscle tone; loss of coordination; the environment (for example, frequent walks on icy stairs); and general health. Thus, the clinician must evaluate all factors concurrently rather than relying upon a single measure.
The velocity of sound propagation has been used successfully to characterize the elastic modulus and breaking strength of engineering materials. Recognizing the potential for application to bone disease, bone biomechanics researchers have shown conclusively that the velocity of sound can be used to assess the elastic modulus and breaking strength of bone, in-vitro. See, W. Abendschein, Hyatt, G. W., "Ultrasonic and Selected Physical Properties of Bone," Clin. Orthop. Rel. Res., 69:294-301, 1970; Ashman, R. B., Cowin, S. C., Van Buskirk, W. C., Rice, J. C., "A Continuous Wave Technique for the Measurement of the Elastic Properties of Cortical Bone," J. Biomechanics, 17(5):349-361, 1984; Ashman, R. B., Rosina, G., Cowin, S. C., Fontenot, M. G., "The Bone Tissue of the Canine Mandible is Elastically Isotropic," J. Biomechanics, 18(9):717-721, 1985; and Ashman, R. B., Corin, J. D., Turner, C. H., "Elastic Properties of Cancellous Bone: Measurement by an Ultrasonic Technique," J. Biomechanics, 20(10):979-986, 1987.
Despite the success of in vitro characterization of bone with velocity, successful in vivo application has remained elusive. Early attempts were made to infer the velocity of long bones from measurements of the frequency of bulk resonance. See, Jurist, J. M., "In Vivo Determination of the Elastic Response of Bone I. Method of Ulnar Resonant Frequency Determination," Phys. Med. Biol., 15(3) 417-426. 1970; Jurist, J. M., "In Vivo Determination of the Elastic Response of Bone II. Ulnar Resonant Frequency in Osteoporotic, Diabetic and Normal Subjects," Phys. Med. Biol., 15(3):427-434, 1970; Fujita, T., et al., "Basic and Clinical Evaluation of the Measurement of Bone Resonant Frequency," Calcif. Tissue Int., 35:153-158, 1983. Only limited success was achieved due to difficulty in controlling major sources of error such as muscle tension, amount of fat and muscle tissue, and complexity of the shape of the long bone. Also, X-ray assessment of the size of the bone was required to accurately determine the length of long bones as a prerequisite to accurate velocity measurements.
More success was achieved with the development of methods for direct measurement of the velocity in peripheral bones. This work began with detection of stress fracture in the metacarpal and metatarsal bones in horses to intervene in the training of race horses before serious fracture occurred. See, e.g., Pratt, G. W., "An In Vivo Method of Ultrasonically Evaluating Bone Strength," Proc. Amer. Assoc. Equine Pract. 26:295-306, 1980; Rabin, D. S., et al., "The Clinical Use of Bone Strength Assessment in the Thoroughbred Race Horse," Proc. Amer. Assoc. Equine Pract., 29:343-351, 1983; and Jeffcot, L. B., et al., "Ultrasound as a Tool for Assessment of Bone Quality in the Horse," Vet. Record, 116:337-342, 1985.
A relationship between the quality of bone and ultrasonic velocity in humans was demonstrated in runners in the 26 mile Boston Marathon. Rubin, C. T., et al., "The Use of Ultrasound In Vivo to Determine Acute Change in the Mechanical Properties of Bone Following Intense Physical Activity," J. Biomechanics, 20(7):723-727, 1987.
A potential clinical application in humans was demonstrated in a study of bone status in premature newborn infants. Wright, L. W., Glade, M. J., Gopal, J., "The Use of Transmission Ultrasonics to Assess Bone Status in the Human Newborn," Pediatric Research, 22(5):541-544, 1987. The study had two components. First, the apparent velocity measured in situ was compared with bone-mineral content (BMC), gestational age and breaking strength in vitro in post-mortem newborns. Second, newborn infants were followed with BMC and ultrasonic analysis. The study demonstrated that velocity of an ultrasonic signal increased linearly with gestational age and correlated well with BMC and breaking strength.
The work disclosed in Gilbert et al., "Correlation Between Transmission Ultrasound and Bone Mass Quantitation Techniques in Postmenopausal Osteoporosis," (abstract), Proc. 33rd Meeting, Soc. Nucl. Med., June, 1986, in which certain teachings of U.S. Pat. No. 4,421,119 to Pratt were used, shows a correlation of ultrasonic velocity of the patella with mass density measured in the spine and wrist.
Although the foregoing methods did indicate that ultrasonic measurement in vivo of bone strength has potential utility, there was no disclosure or suggestion of a device that has clinical utility. Currently available ultrasonic, in vivo bone strength measurement methods are neither accurate nor repeatable. It is important to note that there appears to be a difference of at most 15% in the velocity of cancellous bone, such as the patella, between younger non-osteoporotic and older osteoporotic subjects. Further, the velocity measured in a single bone, such as the patella, varies on the order of 15% depending upon the position of the path of propagation of the wave within the bone. Thus, with present techniques it cannot be predictably determined whether a given result is occasioned by osteoporosis or by variabilities associated with the operation of the measurement equipment.
In addition, currently available techniques do not consider the anisotropic and inhomogenous nature of bone and the number of paths between a sending and receiving transducer that an ultrasonic wave traverses. At present, techniques do not differentiate between paths. Thus, it is an object of the present invention to provide a method and apparatus for locating a desired path through a member, such as a bone, in vivo, and directing an ultrasonic signal along the desired path. It is further an object of the present invention to receive a component of an ultrasonic signal that propagates along a desired path, distinguish it from other components and determine its velocity to provide information about the strength of the member.